Optimization of fragmentation conditions for alpelisib and deuterated abemaciclib in a triple quadrupole mass spectrometer

Abstract

Rak dojke je najčešća zloćudna novotvorina u žena, a njegova prevalencija širom svijeta raste. Personalizirani pristup je bitan dio liječenja, stoga je važno razviti specifične analitičke metode za istraživanje lijekova. Alpelisib i abemaciklib su se pokazali učinkovitim lijekovima u liječenju hormonski ovisnog raka dojke. Oba djeluju na signalne puteve koji su važni za stanični rast i proliferaciju te posljedično, rast tumora. Cilj ovog istraživanja je bio optimizirati uvjete fragmentacije alpelisiba i deuteriranog abemacikliba u trostrukim kvadrupolima dva različita spektrometra masa, Agilent Ultivo i Agilent 6470. Određene su optimalne vrijednosti fragmentorskih napona i kolizijskih energija, te je provedena identifikacija i kvantifikacija ključnih fragmenata specifičnih za ove spojeve. U Agilent Ultivo spektrometru masa uz pozitivnu ionizaciju elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti 442,1 uz fragmetorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 328,0, 114,7, 288,0 i 273,1 uz kolizijske energije od 25, 15 45 i 60 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti 515,2 uz fragmentorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 176,8, 393,0 i 351,3 uz kolizijske energije od 105, 25 i 70 eV. U Agilent 6470 spektrometru masa uz pozitivnu ionizaciju elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti 442,2, uz fragmentorski napon od 140 V. Nastaju fragmentni ioni m/z vrijednosti 328,1 115,0, 288,1, 273,0 i 129,0 uz kolizijske energije od 25, 15, 50, 60 i 105 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti 515,3 uz fragmentorski napon od 120 eV. Nastaju fragmentni ioni od 177,0, 393,1 i 244,9 uz kolizijske energije od 105, 25 i 75 eV. Provedena je analiza i uz negativnu ionizaciju elektroraspršenjem, gdje se ova metoda pokazala manje osjetljivom.Breast cancer is the most common malignant tumor in women, and its prevalence is increasing worldwide. A personalized approach is a crucial part of treatment, making it important to develop specific analytical methods for drug research. Alpelisib and abemaciclib have proven to be effective drugs in the treatment of hormone-dependent breast cancer. Both act on signaling pathways important for cell growth and proliferation, and consequently, tumor growth.The aim of this study was to optimize the fragmentation conditions for alpelisib and deuterated abemaciclib in triple quadrupoles of two different mass spectrometers, the Agilent Ultivo and Agilent 6470. Optimal values for fragmentor voltages and collision energies were determined, and identification and quantification of key fragments specific to these compounds were conducted.In the Agilent Ultivo mass spectrometer with positive electrospray ionization, alpelisib produces a molecular ion with an m/z value of 442,1 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 328,0, 114,7, 288,0, and 273,1 are formed with collision energies of 25, 15, 45, and 60 eV, respectively. Deuterated abemaciclib produces a molecular ion with an m/z value of 515.2 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 176,8, 393,0, and 351,3 are formed with collision energies of 105, 25, and 70 eV, respectively.In the Agilent 6470 mass spectrometer with positive electrospray ionization, alpelisib produces a molecular ion with an m/z value of 442,2 at a fragmentor voltage of 140 V. Fragment ions with m/z values of 328,1, 115,0, 288,1, 273,0 and 129,0 are formed with collision energies of 25, 15, 50, and 105 eV, respectively. Deuterated abemaciclib produces a molecular ion with an m/z value of 515,3 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 177,0, 393,1, and 244,9 are formed with collision energies of 105, 25, and 75 eV, respectively. Analysis was also conducted using negative electrospray ionization, where this method proved to be less sensitive